A Role for Pd(IV) in Catalytic Enantioselective C–H Functionalization with Monoprotected Amino Acid Ligands under Mild Conditions

Abstract

Kinetic and mechanistic studies of the desymmetrization of benzhydrylamine using Pd/monoprotected amino acid ligands (Pd/MPAA) via C-H functionalization with molecular iodine provide mechanistic insight into the rate-determining step and the oxidation state of Pd in the C-H functionalization step. Enantiomeric excess is strikingly insensitive to temperature from ambient temperature up to over 70 °C, and reaction rate is insensitive to the electronic characteristics of the ligand's benzoyl protecting group. The reaction is highly robust with no evidence of catalyst deactivation. Intriguingly, C-H bond breaking does not occur prior to the addition of I to the reaction mixture. Electrochemical experiments demonstrate the viability of oxidative addition of I to Pd(II). Together with F NMR studies, these observations suggest that iodine oxidizes Pd prior to addition of the amine substrate. This work may lead to a better general understanding of the subtle variations in the reaction mechanisms for C-H functionalization reactions that may be extant for this ligand class depending on substrate, amino acid ligand and protecting group, and reaction conditions.

Di-Palladium Complexes are Active Catalysts for Mono-N-Protected Amino Acid Accelerated Enantioselective C-H Functionalization

“…22 Despite the many exciting developments in Pd-MPAA methodology and several experimental and computational studies aimed at understanding these reactions, the structures of Pd-MPAA catalysts remains unclear in most cases. In a notable exception to this trend, a recent kinetic, spectroscopic, and computational study of MPAA-accelerated C-H iodination reactions 23,24 provided experimental data consistent with a previously reported [25][26][27][28] structural model featuring mono-nuclear Pd intermediates with di-anionic κ 2 -(N,O)-bound MPAA ligands ( Figure 2B). Given the general structural ambiguity surrounding Pd-MPAA catalysis, mechanistic models generally defer to the widely-held notion that MPAA ligands coordinate mono-palladium species by di-or mono-anionic chelation (Figure 2A and B, respectively).…”

Visual kinetic analysis

“…VTNA has already been used successfully by academic and industrial research groups in metal-catalysed [25][26][27][28][29][30][31][32][33][34][35][36][37][38] and organocatalytic reactions. [39][40][41][42][43]…”

s-Block metal scorpionates – A new sodium hydrido-tris(3,5-dimethyl-1-pyrazolyl)borate salt showing an unusual core stabilized by bridging and terminal O-bonded DMSO ligands

“…In our opinion, the most remarkable structural feature of 2 resides in the coordination of the sodium atom Na2 by six molecules of DMSO. To the best of our knowledge, previously such a fragment has been only observed once (based on a CDS query), and attributed to the polymeric edifice [Na 4 (DMSO) 15 ][(I 3 ) 3 (I)] (refcodes: ITITAH, KAZWAM) (Duarte-Ruiz et al, 2011;Plata et al, 2017). Therefore, the structure of the cationic moiety [Na 2 Tp * (μ-Me 2 SO) 3 (Me 2 SO) 3 ] + can be considered as unprecedented for a discrete complex.…”